Abstract
Type III IFNs (IFN-λs) constitute a new subfamily with antiviral activities by signaling through a unique receptor complex composed of IFN-λs receptor 1 (IFNλR1) and interleukin-10 receptor 2 (IL10R2). As tree shrews (Tupaia belangeri) have shown susceptiblility to several human viruses, they are a potentially important model for analyzing viral infection. However, little is known about their IFN-λs system. We used the tree shrew genome to retrieve IFN-λs and their receptor contig sequences by BLASTN and BLASTZ algorithms, and GenScan was used to scan transcripts from the putative contig sequences. RT-PCR and bioinformatic methods were then used to clone and characterize the IFN-λs system. Due to its highest identity with human IFN-λ3, we opted to define one intact IFN-λ gene, tsIFN-λ3, as well as its two receptor subunits, tsIFNλR1 and tsIL10R2. Additionally, our results showed that tsIFN-λ3 contained many features conserved in IFN-λ3 genes from other mammals, including conserved signal peptide cleavage and glycosylation sites, and several residues responsible for binding to the type III IFNR. We also found six transcript variants in the receptors: three in tsIFNλR1, wherein different extracellular regions exist in three transmembrane proteins, resulting in different affinities with IFN-λs; and three more variants in tsIL10R2, encoding one transmembrane and two soluble proteins. Based on tissue distribution in the liver, heart, brain, lung, intestine, kidney, spleen, and stomach, we found that IFN-λs receptor complex was expressed in a variety of organs although the expression level differed markedly between them. As the first study to find transcript variants in IL-10R2, our study offers novel insights that may have important implications for the role of IFN-λs in tree shrews’ susceptibility with a variety of human viruses, bolstering the arguments for using tree shrews as an animal model in the study of human viral infections.
Highlights
In 2003, type III interferons (IFNs), known as IFN-ls, were described as members of a new cytokine family [1,2]
Three IFN-l genes have been identified: IFN-l1 (IL29), IFN-l2 (IL-28A) and IFN-l3 (IL-28B); IFN-l1 is a pseudogene in mouse [1,2,7,12,13], four functional and one pseudo- IFN-l (IFN-l4) genes are present in Xenopus [14], and two functional IFN-l genes in bats which are conserved with other mammalian IFN-l sequences [15]
Though IFN-ls have been shown to exist in several mammals, there is relatively little information regarding their presence in tree shrews (Tupaia belangeri), a squirrel-like mammal with similarities to primitive primates
Summary
In 2003, type III interferons (IFNs), known as IFN-ls, were described as members of a new cytokine family [1,2]. Signaling through a heterodimeric class II cytokine receptor, IFN-lR1 (IL28RA) and IL-10R2 (IL-10RB), IFN-ls play an essential role in the induction of an antiviral state and contribute to the initiation of adaptive immune response, similar to type I IFNs [1,2,3,4,5,6,7,8,9,10,11]. IFN-ls have been characterized in mice, zebrafish, chickens, bats, pigs, and Xenopus and different species had various numbers of the IFN-l gene. Likewise two IFN-l genes, IFN-l1 and IFN-l3, were characterized in pigs [16,17], while chickens and zebrafish express only a single IFN-l [18,19,20,21]. Though IFN-ls have been shown to exist in several mammals, there is relatively little information regarding their presence in tree shrews (Tupaia belangeri), a squirrel-like mammal with similarities to primitive primates
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